ID   UGDH_DROME              Reviewed;         476 AA.
AC   O02373; O02647; Q9VRZ9;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1997, sequence version 1.
DT   27-MAR-2024, entry version 182.
DE   RecName: Full=UDP-glucose 6-dehydrogenase;
DE            Short=UDP-Glc dehydrogenase;
DE            Short=UDP-GlcDH;
DE            Short=UDPGDH;
DE            EC=1.1.1.22;
DE   AltName: Full=Protein sugarless;
DE   AltName: Full=Protein suppenkasper;
GN   Name=sgl; Synonyms=kiwi, ska; ORFNames=CG10072;
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND
RP   DISRUPTION PHENOTYPE.
RX   PubMed=9217004; DOI=10.1242/dev.124.13.2623;
RA   Binari R.C., Staveley B.E., Johnson W.A., Godavarti R., Sasisekharan R.,
RA   Manoukian A.S.;
RT   "Genetic evidence that heparin-like glycosaminoglycans are involved in
RT   wingless signaling.";
RL   Development 124:2623-2632(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX   PubMed=9342049; DOI=10.1242/dev.124.18.3565;
RA   Haecker U., Lin X., Perrimon N.;
RT   "The Drosophila sugarless gene modulates Wingless signaling and encodes an
RT   enzyme involved in polysaccharide biosynthesis.";
RL   Development 124:3565-3573(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=9272947; DOI=10.1242/dev.124.16.3055;
RA   Haerry T.E., Heslip T.R., Marsh J.L., O'Connor M.B.;
RT   "Defects in glucuronate biosynthesis disrupt Wingless signaling in
RT   Drosophila.";
RL   Development 124:3055-3064(1997).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-76.
RC   STRAIN=Canton-S;
RA   Benevolenskaya E.V., Frolov M.V., Birchler J.A.;
RT   "Mutation in the Drosophila gene encoding UDP-glucose dehydrogenase affects
RT   expression of unlinked genes.";
RL   Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley;
RX   PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA   Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA   Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA   George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA   Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA   Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA   Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA   An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA   Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA   Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA   Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA   Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA   Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA   Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA   Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA   Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA   Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA   Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA   Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA   Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA   Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA   Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA   McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA   Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA   Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA   Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA   Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA   Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA   Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA   Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA   Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA   Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA   Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA   Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA   Venter J.C.;
RT   "The genome sequence of Drosophila melanogaster.";
RL   Science 287:2185-2195(2000).
RN   [6]
RP   GENOME REANNOTATION.
RC   STRAIN=Berkeley;
RX   PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA   Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA   Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA   Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA   Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA   Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA   Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT   "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT   review.";
RL   Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley; TISSUE=Embryo;
RX   PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA   Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA   Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA   Celniker S.E.;
RT   "A Drosophila full-length cDNA resource.";
RL   Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
CC   -!- FUNCTION: Involved in the biosynthesis of glycosaminoglycans;
CC       hyaluronan, chondroitin sulfate and heparan sulfate. Required for
CC       wingless signaling in different tissues. {ECO:0000269|PubMed:9217004,
CC       ECO:0000269|PubMed:9272947, ECO:0000269|PubMed:9342049}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + 2 NAD(+) + UDP-alpha-D-glucose = 3 H(+) + 2 NADH + UDP-
CC         alpha-D-glucuronate; Xref=Rhea:RHEA:23596, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC         ChEBI:CHEBI:58052, ChEBI:CHEBI:58885; EC=1.1.1.22;
CC         Evidence={ECO:0000269|PubMed:9217004};
CC   -!- PATHWAY: Nucleotide-sugar biosynthesis; UDP-alpha-D-glucuronate
CC       biosynthesis; UDP-alpha-D-glucuronate from UDP-alpha-D-glucose: step
CC       1/1. {ECO:0000269|PubMed:9217004}.
CC   -!- DISRUPTION PHENOTYPE: 'Wingless-like' cuticular phenotype; reduced
CC       growth of imaginal disks and pattern defects.
CC       {ECO:0000269|PubMed:9217004, ECO:0000269|PubMed:9272947}.
CC   -!- SIMILARITY: Belongs to the UDP-glucose/GDP-mannose dehydrogenase
CC       family. {ECO:0000305}.
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DR   EMBL; AF007870; AAB63208.1; -; mRNA.
DR   EMBL; AF000570; AAB58714.1; -; mRNA.
DR   EMBL; AF009013; AAB63462.1; -; mRNA.
DR   EMBL; AF001310; AAC97125.1; -; mRNA.
DR   EMBL; AH007072; AAC97126.1; -; Genomic_DNA.
DR   EMBL; AE014296; AAF50631.1; -; Genomic_DNA.
DR   EMBL; AY052137; AAK93561.1; -; mRNA.
DR   RefSeq; NP_476980.1; NM_057632.4.
DR   AlphaFoldDB; O02373; -.
DR   SMR; O02373; -.
DR   BioGRID; 64209; 9.
DR   IntAct; O02373; 1.
DR   STRING; 7227.FBpp0076647; -.
DR   PaxDb; 7227-FBpp0076647; -.
DR   DNASU; 38760; -.
DR   EnsemblMetazoa; FBtr0076938; FBpp0076647; FBgn0261445.
DR   GeneID; 38760; -.
DR   KEGG; dme:Dmel_CG10072; -.
DR   AGR; FB:FBgn0261445; -.
DR   CTD; 24054; -.
DR   FlyBase; FBgn0261445; sgl.
DR   VEuPathDB; VectorBase:FBgn0261445; -.
DR   eggNOG; KOG2666; Eukaryota.
DR   HOGENOM; CLU_023810_7_0_1; -.
DR   InParanoid; O02373; -.
DR   OMA; CFIAVGT; -.
DR   OrthoDB; 167209at2759; -.
DR   PhylomeDB; O02373; -.
DR   Reactome; R-DME-173599; Formation of the active cofactor, UDP-glucuronate.
DR   SignaLink; O02373; -.
DR   UniPathway; UPA00038; UER00491.
DR   BioGRID-ORCS; 38760; 0 hits in 1 CRISPR screen.
DR   GenomeRNAi; 38760; -.
DR   PRO; PR:O02373; -.
DR   Proteomes; UP000000803; Chromosome 3L.
DR   Bgee; FBgn0261445; Expressed in thoracico-abdominal ganglion (Drosophila) and 57 other cell types or tissues.
DR   ExpressionAtlas; O02373; baseline and differential.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR   GO; GO:0003979; F:UDP-glucose 6-dehydrogenase activity; IMP:UniProtKB.
DR   GO; GO:0030206; P:chondroitin sulfate biosynthetic process; IMP:UniProtKB.
DR   GO; GO:0007427; P:epithelial cell migration, open tracheal system; IMP:UniProtKB.
DR   GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IMP:UniProtKB.
DR   GO; GO:0006024; P:glycosaminoglycan biosynthetic process; IMP:UniProtKB.
DR   GO; GO:0015014; P:heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process; IMP:UniProtKB.
DR   GO; GO:0007509; P:mesoderm migration involved in gastrulation; IMP:UniProtKB.
DR   GO; GO:0007367; P:segment polarity determination; IMP:FlyBase.
DR   GO; GO:0006065; P:UDP-glucuronate biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR   Gene3D; 1.20.5.100; Cytochrome c1, transmembrane anchor, C-terminal; 1.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 2.
DR   InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR017476; UDP-Glc/GDP-Man.
DR   InterPro; IPR014027; UDP-Glc/GDP-Man_DH_C.
DR   InterPro; IPR036220; UDP-Glc/GDP-Man_DH_C_sf.
DR   InterPro; IPR014026; UDP-Glc/GDP-Man_DH_dimer.
DR   InterPro; IPR001732; UDP-Glc/GDP-Man_DH_N.
DR   InterPro; IPR028356; UDPglc_DH_euk.
DR   NCBIfam; TIGR03026; NDP-sugDHase; 1.
DR   PANTHER; PTHR11374:SF3; UDP-GLUCOSE 6-DEHYDROGENASE; 1.
DR   PANTHER; PTHR11374; UDP-GLUCOSE DEHYDROGENASE/UDP-MANNAC DEHYDROGENASE; 1.
DR   Pfam; PF00984; UDPG_MGDP_dh; 1.
DR   Pfam; PF03720; UDPG_MGDP_dh_C; 1.
DR   Pfam; PF03721; UDPG_MGDP_dh_N; 1.
DR   PIRSF; PIRSF500133; UDPglc_DH_euk; 1.
DR   PIRSF; PIRSF000124; UDPglc_GDPman_dh; 1.
DR   SMART; SM00984; UDPG_MGDP_dh_C; 1.
DR   SUPFAM; SSF48179; 6-phosphogluconate dehydrogenase C-terminal domain-like; 1.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   SUPFAM; SSF52413; UDP-glucose/GDP-mannose dehydrogenase C-terminal domain; 1.
DR   Genevisible; O02373; DM.
PE   1: Evidence at protein level;
KW   NAD; Oxidoreductase; Reference proteome; Wnt signaling pathway.
FT   CHAIN           1..476
FT                   /note="UDP-glucose 6-dehydrogenase"
FT                   /id="PRO_0000074064"
FT   ACT_SITE        272
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:O60701"
FT   BINDING         7..12
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:O60701"
FT   BINDING         32
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:O60701"
FT   BINDING         37
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:O60701"
FT   BINDING         85..89
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:O60701"
FT   BINDING         126..127
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:O60701"
FT   BINDING         157..161
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:O60701"
FT   BINDING         161
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:O60701"
FT   BINDING         216..220
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:O60701"
FT   BINDING         256
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:O60701"
FT   BINDING         263..269
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:O60701"
FT   BINDING         272..275
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:O60701"
FT   BINDING         334..335
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:O60701"
FT   BINDING         342
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:O60701"
FT   BINDING         439
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:O60701"
FT   CONFLICT        59
FT                   /note="K -> R (in Ref. 3; AAC97125)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   476 AA;  52875 MW;  1450B9A0C802BBE7 CRC64;
     MKVCCIGAGY VGGPTCAVMA LKCPDIVITL VDKSSERIAQ WNSDKLPIYE PGLDEVVKKC
     RNVNLFFSTD IETAIKEADL IFISVNTPTK TCGNGKGRAA DLKYVESAAR MIAEIAQSNK
     IVVEKSTVPV RAAESIMHIL RANQKPGIHY DILSNPEFLA EGTAINDLLN ADRVLIGGEE
     TPEGHQAVEK LSWIYEHWIP KQNILTTNTW SSELSKLAAN AFLAQRISSI NSLSAVCEAT
     GADVSEVARA VGLDSRIGSK FLQASVGFGG SCFQKDILNL IYICENLNLP EVAAYWQQVI
     DMNEYQKRRF SQKIIESLFN TVSDKRIAIL GFAFKKNTGD TRETAAITVC QTLLEEGAAL
     DIYDPKVEPE QIIDDLTHPS VTESPEKVKK AVQIHSDPYS AVRATHALVI CTEWDEFVDL
     DFKRIYQSMM KPAYIFDGRK ILDHERLQQI GFHVQTIGKK YQRTGLLRSW GIVPQL
//